三氧化二砷诱导小细胞肺癌细胞凋亡及p53、bcl-2基因表达的研究

Arsenic trioxide induced apoptosis and expression of p53 and bcl-2 genes in human small cell lung cancer cells

目的 研究三氧化二砷 (As2 O3)诱导小细胞肺癌细胞凋亡及其机制。方法 采用末端脱氧核苷酰转移 (TUNEL)法检测细胞凋亡 ,免疫组织化学 (SABC)法分析As2 O3对小细胞肺癌细胞(NeI H细胞 )p5 3、bcl 2基因蛋白表达的影响。结果 As2 O30 5 μmol/L、1 0 μmol/L、2 0 μmol/L作用72h ,NeI H细胞均可呈现凋亡所特有的亚G1峰 ,凋亡比率随药物作用浓度增加和作用时间延长而增高。实验组p5 3基因蛋白表达较对照组明显增多 ,药物浓度越高表达越多 (P =0 0 0 1) ;bcl 2基因蛋白表达较对照组明显减少 ,药物作用浓度越高表达越少 (P =0 0 0 1)。结论 As2 O3抗肿瘤作用主要是通过诱导细胞凋亡实现的 ,其机制与上调p5 3基因表达及下调bcl

Objective To study the arsenic trioxide (As 2O 3 ) induced apoptosis in a human small cell lung cancer cell line (NeI H cells) and its possible mechanisms Methods Apoptotic cells were detected by the TUNEL method The expression of p53 and bcl 2 was analyzed with immunohistochemical staining Results NeI H cells showed the sub G 1 peak after treatment with As 2O 3 (0 5 μmol/L,1 0 μmol/L, and 2 0 μmol/L )for 72 hours The ratio of apoptotic cells increased with the increasing concentrations of the drug and the time of culture Immunohistochemical staining of NeI H cells showed increased expression of p53, but decreased expression of bcl 2 with the increasing concentrations of the drug Conclusion The anti carcinogenic effect of As 2O 3 is due to the induction of cell apoptosis Up regulation of the p53 gene and down regulation of the bcl 2 gene may be an underlining mechanism